Regulation of mouse liver flavin-containing monooxygenases 1 and 3 by sex steroids
Regulation of mouse liver flavin-containing monooxygenases 1 and 3 by sex steroids
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DOI：
10.1006/abbi.1997.9965
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发表时间：
1997-06-15
影响因子：
3.9
通讯作者：
Hodgson, E
中科院分区：
文献类型：
--
作者：
Falls, JG;Ryu, DY;Hodgson, E
基于酶活性、蛋白质水平和 mRNA 水平，我们之前已经证明了 FMO 形式 1、3 和 5 在小鼠肝脏中分别具有雌性主导、雌性特异性和性别无关的表达。本研究调查了睾酮、17β-雌二醇和黄体酮在肝脏 FMO 调节中的作用。在性腺切除的 CD-1 小鼠、接受激素植入的正常 CD-1 小鼠和接受各种激素治疗的性腺切除的小鼠中检查了 FMO 表达。男性去势后，肝脏FMO活性水平显着升高，血清睾酮水平显着降低；然而，对阉割动物施用生理水平的睾酮后，FMO 活性和睾酮浓度恢复到对照水平。当性完整和卵巢切除的雌性小鼠接受睾酮治疗时，它们的肝脏 FMO 活性水平降低至雄性小鼠的水平，同时血清睾酮水平较高。在雄性中，去势显着增加了 FMO3 和 FMO1 的表达，而对去势雄性进行睾酮替代会导致 FMO3 表达的消除。此外，对雌性（性完整和性腺切除的动物）施用睾酮可减少 FMO1 表达并消除 FMO3 表达。在女性中，单独卵巢切除术会略微降低 FMO 活性，表明女性性类固醇可能具有刺激作用；然而，女性FMO同工酶表达相对不变，对卵巢切除女性的激素替代疗法没有明显效果。在男性和女性中，FMO5 水平不受性腺切除术或激素施用的影响，因此表明该异构体具有独立于性激素的调节机制。有趣的是，在性完整的男性中，经过 17 β-雌二醇治疗后，FMO1 蛋白水平有所增加。然而，仅观察到 FMO3 蛋白水平略有增加。没有发现女性 FMO 表达的阳性激素效应物。 (C) 1997 年学术出版社。
Based on enzyme activity, protein levels, and mRNA levels, we have previously demonstrated the female-predominant, female-specific, and gender-independent expression in mouse liver of FMO forms 1, 3, and 5, respectively. This study investigated the roles of testosterone, 17 beta-estradiol, and progesterone in the regulation of hepatic FMOs. FMO expression was examined in gonadectomized CD-1 mice, normal CD-1 mice receiving hormonal implants, and gonadectomized mice receiving various hormonal treatments. Following castration of males, hepatic FMO activity levels were significantly increased and serum testosterone levels significantly decreased; however, administration of physiological levels of testosterone to castrated animals returned FMO activity and testosterone concentrations to control levels. When sexually intact and ovariectomized female mice were treated with testosterone, their hepatic FMO activity levels were reduced to those of their male counterparts, concomitant with high serum testosterone levels. In males, castration dramatically increased FMO3 and FMO1 expression, and testosterone replacement to castrated males resulted in ablation of FMO3 expression. In addition, testosterone administration to females (sexually intact and gonadectomized animals) reduced FMO1 expression and obviated FMO3 expression. In females, ovariectomy alone slightly reduced FMO activity, indicative of a possible stimulatory role of female sex steroids; however, female FMO isozyme expression was relatively unchanged, and hormone replacement therapy to ovariectomized females had no discernible effect. In males and females, FMO5 levels were unaffected by gonadectomy or hormone administration, thus indicating a sex hormone-independent mechanism of regulation for this isoform. Interestingly, FMO1 protein levels were increased in sexually intact males following treatment with 17 beta-estradiol; however, only a slight increase in FMO3 protein level was observed. No positive hormone effecters of female FMO expression were identified. (C) 1997 Academic Press.